For regionally-advanced and metastatic carcinoma (Ca) of the breast, combination chemotherapy may help to achieve local control and improved survival and is used in Project A to shrink primary masses and treat overt or micrometastases. Twenty-two pts (11 stage III, II stage IV) were treated with combination chemotherapy. Sixteen of 20 responders underwent surgery for local control. All 10 with inflammatory Ca had elimination of the inflammatory component. Many combinations are available for recurrent or metastatic disease, but few prospective trials compare the regimens and stratify for the prognostic variables. Project B compared 3 regimens for response rates, duration of survival, and the effect of MER immunotherapy. A group effort was necessary to stratify for the variables. With 380 pts entered, prior postoperative adjuvant radiotherapy and immunotherapy were shown to be detrimental factors for response and survival. Chemotherapy containing doxorubicin is shown to be superior. New drug combinations are needed to treat pts with tumors refractory to standard drugs. Projects C and D are two new combinations of mitomycin-C and vinblastine, and doxorubicin and VP 16 respectively. With 29 and 24 pts entered, both are highly active combinations.